The recent development of hemodialytic therapy has now greatly reduced death caused directly by chronic renal failure. Suitable therapy for chronic and renal failure has made it possible to live for another 20 year or longer. Accordingly, it has become extremely important to improve the quality of life (hereinafter referred to as QOL) of patients (that is, to let patients live an ordinary life without being physically handicapped or socially isolated. Therefore, at present, it is desirable to take measures against the complications of chronic renal failure from which patients may suffer while living for a long period of time and also undertake suitable therapeutic means for ensuring the patients' early rehabilitation in society.
Chronic renal failure exhibits a decrease in the number of nephrons irrespective of the type of renal disorder. The extended decrease in the number of nephrons results in the loss of renal function, which necessitates artificial dialysis. Renal depression due to a decrease in the number of nephrons causes a decrease in serum Ca, a decrease in the production of active vitamin D, elevation of the serum Ca set-point at which the secretion of parathyroid hormone (hereinafter referred to as PTH) is set to be suppressed, a decrease in the number of parathyroid-activated vitamin D receptors, the metabolic disorder involving phosphorus, etc., causing hypersecretion of PTH that may be followed by secondary hyperparathyroidism.
PTH is indispensable for the regulation of the metabolism of calcium and phosphorus, while having a great influence on the stable maintenance of bone. Hypersecretion of PTH acts on bone, thereby causing fibrous osteitis. It is said that PTH is one of uremic substances which cause anemia, organic ulcers, central nervous neuropathy, itching, hyperlipemia, etc. and it is a significant factor in the presentation of the symptoms of renal osteodystrophy which is a severe complication for patients subjected to artificial dialysis. Many patients who have once suffered from the disorder of renal osteodystrophy are difficult to cure, and the disorder noticeably lowers with the QOL for patients subjected to artificial dialysis.
It is said that most patients with light renal failure suffer from secondary hyperparathyroidism. The frequency and the degree of the complication increase in patients who are subjected to artificial dialysis for a long period of time. Therefore, it is necessary to prevent the complication in the early stages of renal failure.
To cure secondary hyperparathyroidism, for example, activated vitamin D preparations are administrated to patients with hypocalcemia or those with insufficiency of vitamin D production. However, such preparations involve harmful side effects in that they often cause hypercalcemia and ectopic calcification. Pulse therapy may be administered to patients resistant to activated vitamin D preparations. However, pulse therapy is problematic in that it may cause hypometabolic turnover osteitis, etc., in addition to the above-mentioned disadvantages. In order to lower the serum Ca set-point at which the secretion of PTH is set to be suppressed, activated vitamin D preparations and calcium preparations may be employed, which, however, are still problematic for the above reasons. On the other hand, aluminum hydroxide is a chemical that should not be administered to patients with hyperphosphatemia caused by the metabolic disorder of phosphorus, who are subjected to artificial dialysis. Therefore, in place of this, calcium carbonate or calcium acetate preparations are administered to them. However, because of poor phosphorus adsorbability, calcium preparations must be administered in large quantities, resulting in a high risk of hypercalcemia. Low-protein dietary cure may also be employed with the limitation of phosphorus. However, low-protein diets often bring about negative results of trophopathy and hypercatabolism. Surgical treatment of an enucleating parathyroid gland may be employed, which, however, brings about serious mental and physical strains on patients.
As mentioned hereinabove, the conventional therapeutic means for hyperparathyroidism are all problematic. In particular, for patients subjected to artificial dialysis for a long period of time, even the combinations of such means produce unsatisfactory therapeutic effects at present.